Ataxia and Purkinje cell degeneration in mice lacking the CAMTA1 transcription factor

Chengzu Long, Chad E. Grueter, Kunhua Song, Song Qin, Xiaoxia Qi, Y. Megan Kong, John M. Shelton, James A. Richardson, Chun Li Zhang, Rhonda Bassel-Duby, Eric N. Olson

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Members of the calmodulin-binding transcription activator (CAMTA) family of proteins function as calcium-sensitive regulators of gene expression in multicellular organisms ranging from plants to humans. Here, we show that global or nervous system deletion of CAMTA1 in mice causes severe ataxia with Purkinje cell degeneration and cerebellar atrophy, partially resembling the consequences of haploinsufficiency of the human CAMTA1 locus. Gene-expression analysis identified a large collection of neuronal genes that were dysregulated in the brains of CAMTA1-mutant mice, and elucidation of a consensus sequence for binding of CAMTA proteins to DNA revealed the association of CAMTA-binding sites with many of these genes. We conclude that CAMTA1 plays an essential role in the control of Purkinje cell function and survival. CAMTA1-mutant mice provide a model to study the molecular mechanisms of neurodegenerative diseases and for screening potential therapeutic interventions for such disorders.

Original languageEnglish (US)
Pages (from-to)11521-11526
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number31
DOIs
Publication statusPublished - Aug 5 2014

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Keywords

  • CAMTA2
  • Dimerization
  • Neural genes
  • Palindromic DNA

ASJC Scopus subject areas

  • General

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